Consider Using Ketamine When Appropriate—If Managed Carefully, the Benefits will Usually Outweigh the Potential Side Effects



Consider Using Ketamine When Appropriate—If Managed Carefully, the Benefits will Usually Outweigh the Potential Side Effects


Elizabeth E. Costello MD



In 1970, 8 years after it was first synthesized, ketamine was released for clinical use in the United States. Initially ketamine was believed to be the “ideal” anesthetic, providing amnesia, analgesia, immobility, and loss of consciousness. Shortly after its use became widespread, however, there were many reports of patients emerging from anesthesia with hallucinations and recalling vivid dreams. The discovery of “emergence reactions” led many practitioners to avoid using ketamine for routine cases. However, ketamine remains an important tool in the anesthesiologist’s armamentarium, as it is a versatile drug that can be given by almost any route and can provide analgesia, sedation, or general anesthesia depending on the dose administered. Originally, ketamine was indicated as an anesthetic as well as an analgesic for cardiac surgery, trauma, obstetric analgesia, as well as for dressing changes in burns patients.

Ketamine is different from other anesthetics in that it induces a state of dissociate anesthesia, whereby higher centers in the brain are unable to perceive auditory, visual, or painful stimuli. There is a dose-related loss of consciousness and profound analgesia. Patients’ eyes remain open and they often maintain reflexes, although corneal, cough, and swallow reflexes cannot be assumed to be protective. In addition, patients have anterograde amnesia and have no recall of surgical procedures. There is a rapid onset of action, as the drug crosses the blood-brain barrier quickly secondary to low molecular weight, high lipid solubility, and a pKa near physiologic pH. Following intravenous (IV) administration, onset is seen in 30 seconds, with peak action in 60 seconds. The anesthetic effects of ketamine following a usual induction dose (1 to 2 mg/kg) remain for 10 to 15 minutes only. Drug plasma levels required for anesthesia and amnesia are 0.7 to 2.2 mcg/mL, with awakening occurring at levels of 0.5 mcg/mL. Although the anesthetic duration of action of ketamine is short, the analgesic effects last much longer, as a plasma level of only 0.1 mcg/mL is required for analgesic effects to be seen.

Ketamine interacts with N-methyl-D-aspartate (NMDA), opioid, nicotinic, muscarinic and calcium-channel receptors. It is the antagonistic action
at NMDA receptors that produces the majority of ketamine’s effects, including analgesia, amnesia, and the psychomimetic side effects. It also has effects on both central and spinal opioid receptors, with µ-receptors contributing to analgesia and κ-receptors to the psychomimetic effects. On a larger scale, ketamine leads to inhibition of thalamocortical pathways and stimulation of the limbic system.

Ketamine acts differently from other anesthetic drugs in relation to both the respiratory and cardiac systems. Ketamine does not depress respiration unless it is given in a large rapid bolus, and CO2 responsiveness is maintained at or close to normal levels. The major respiratory advantage of ketamine is that it causes profound bronchodilation, to the same degree as inhalation agents. This makes ketamine an excellent choice of induction agent in asthmatic patients. It has even been used to treat refractory cases of status asthmaticus.

Unlike other anesthetic agents, ketamine does not depress the cardiac system. On induction with ketamine, increases in heart rate, blood pressure, and cardiac output are seen. The mechanism of the cardiovascular effects is sympathetic stimulation and inhibition of both intraneuronal and extraneuronal uptake of catecholamines. Because it is indirect stimulation that leads to these effects, in the catecholamine-depleted patient, ketamine can have the opposite effect, as the drug also has a direct myocardial depressant effect that is normally masked by its sympathetic activity. Ketamine’s effects on the heart lead to an increase in cardiac oxygen consumption, thus making it a poor choice for patients with ischemic cardiac disease. Patients with pulmonary hypertension are also poor candidates for ketamine, as the drug causes a greater increase in pulmonary vascular resistance than systemic vascular resistance.

A variety of patients can benefit from the use of ketamine as an induction agent, especially ASA class 4 patients with respiratory and cardiac dysfunction, excluding cardiac ischemia. The bronchodilating effects of ketamine make it particularly helpful for patients with severe bronchospastic disease. The other niche where ketamine has been found to be interesting is with patients with hemodynamic compromise secondary to hypovolemia or cardiomyopathy. This includes such diagnoses as sepsis, trauma, cardiac tamponade, and restrictive pericarditis. The only caveat is that if these patients are catecholamine-depleted, the direct myocardial depressant effects may be seen. In tamponade, the benefit of ketamine is that it maintains the heart rate and right atrial filling pressures through its sympathetic stimulation. Patients who require frequent, brief procedures, such as burn patients undergoing dressing changes, can benefit from the use of ketamine as a sedative, because subanesthetic doses can be used with good analgesia and rapid return to normal function. It can be used as an adjunct to regional
anesthesia, as a sedative prior to painful blocks, or to position patients already in pain. The main advantage is the profound analgesia without respiratory depression or hypotension. Because of these properties, ketamine is useful in emergency medicine, war zones, entrapment situations, and high-altitude anesthesia.

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Jul 1, 2016 | Posted by in ANESTHESIA | Comments Off on Consider Using Ketamine When Appropriate—If Managed Carefully, the Benefits will Usually Outweigh the Potential Side Effects
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